Glucagon potentiates intestinal reperfusion injury.
Vasoactive agents, including glucagon, have been used in treatment of mesenteric ischemia. Such drugs change both intestinal blood flow and metabolism. Since reperfusion injury reflects the metabolic state of an organ as well as the duration and severity of ischemia, we investigated the effect of glucagon in a standard model of intestinal ischemia. Data were generated from denervated isoperfused rat small intestinal preparations (n = 39). Arterial and venous pressures, intestinal blood flow, and oxygen consumption were monitored. Animals were subjected to 15, 30, or 45 minutes of ischemia followed by 1 hour reperfusion. Experiments were performed without drug infusion or during intravenous glucagon administration (0.1, 0.2, or 0.4 micrograms/kg/min). After the rats were killed, histologic sections of intestine were graded 1 through 5 in a blinded fashion with 1 = normal villi and 5 = severe injury. Results (mean +/- SD) were analyzed by analysis of variance (*p less than 0.05). Glucagon at all concentrations increased intestinal blood flow and oxygen consumption before ischemia. For example, with 0.2 micrograms/kg/min glucagon, intestinal blood flow increased from 80.78 +/- 13.5 to 114.79 +/- 21.02 ml/min.100 gm* and oxygen consumption increased from 3.65 +/- 0.73 to 5.73 +/- 1.37 ml/min.100 gm.* Mucosal injury after ischemia reflected duration of ischemia and glucagon infusion rate. At all ischemic intervals, increased glucagon concentrations were associated with greater mucosal injury. In fact the histologic injury with 15 minutes of ischemia + 0.2 microgram/kg/min glucagon (3.04 +/- 0.49) exceeded that of 30 minutes of ischemia (2.87 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
Clark
E T
ET
Department of Surgery, University of Chicago, IL 60637.
Gewertz
B L
BL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005934:Glucagon / Q000009:adverse effects / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015424:Reperfusion / Q000295:instrumentation / Q000379:methods; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D005934:Glucagon